Multiple sclerosis (MS) is characterized pathologically by scattered areas of inflammation, demyelination, and axonal pathology affecting the brain, optic nerves, and spinal cord. Individual episodes of inflammatory demyelination may be accompanied by clinical symptoms, termed relapses, followed in most cases by clinical recovery; the resulting pattern of relapse-remission is seen early in disease in most patients.
It is widely believed that the clinical manifestations of MS are mediated by immune-initiated inflammatory demyelination and axonal injury. The brain shows hallmarks of an immunopathologic process including perivascular infiltration by lymphocytes and monocytes, class II MHC antigen expression by cells in the lesions, and cytokine and chemokines secretion by activated cells.
Epidemiologic studies suggest both environmental and genetic factors in the pathogenesis of MS. The geographic distribution of the disease suggests environmental factors or perhaps dietary factors. Worldwide prevalence differs according to geography. The prevalence of MS in the northern United States, Canada and northern Europe is at least 100 per 100,000 persons; in certain regions the prevalence of MS exceeds 300 per 100,000 persons, compared with less than 10 per 100,000 persons in Japan and China.
MS produces numerous neurologic symptoms and signs including damage of the optic nerves, pyramidal tracts, posterior columns, cerebellum, and of the central vestibular system of medial longitudinal fasciculus. Older patients develop progressive spastic leg weakness, axial instability, and bladder impairment. Visual symptoms, sensory symptoms and gait or balance disturbances are frequent symptoms in MS.
Pharmacotherapy of MS includes corticosteroids such as methylprednisolone, interferon β-1a and interferon β-1b, glatiramer acetate, natalizumab and immunosuppressants such as methotrexate and mitoxantrone. These agents have some beneficial effect on the intensity and frequency of the relapses in some of MS patients. However, their side effects reduce patient's compliance.
International Patent Publication Nos. WO 03/017920 and WO 2005/090387 of the applicant of the present invention have demonstrated the beneficial effect of a 9-mer peptide, designated 3 ml or IIIM1, derived from histone H2A on an experimental model of MS. Both intravenous and oral administrations of the peptide significantly ameliorated the neurological symptoms in the diseased mice. IIIM1 was also shown to be active in other experimental MS systems such as mouse adoptive transfer and rat EAE models.
There is still an unmet need for improved medicaments to treat inflammatory and autoimmune diseases such as, for example, multiple sclerosis.